Noncanonical function of folate through folate receptor 1 during neural tube formation.

Folate supplementation reduces the occurrence of neural tube defects (NTDs), birth defects consisting in the failure of the neural tube to form and close. The mechanisms underlying NTDs and their prevention by folate remain unclear. Here we show that folate receptor 1 (FOLR1) is necessary for the formation of neural tube-like structures in human-cell derived neural organoids.

Non-canonical function of folate/folate receptor 1 during neural tube formation.

Folate supplementation reduces the occurrence of neural tube defects, one of the most common and serious birth defects, consisting in the failure of the neural tube to form and close early in pregnancy. The mechanisms underlying neural tube defects and folate action during neural tube formation remain unclear. Here we show that folate receptor 1 (FOLR1) is necessary for the formation of neural tube-like structures in human-cell derived neural organoids.

Calcium dynamics at the neural cell primary cilium regulate Hedgehog signaling-dependent neurogenesis in the embryonic neural tube.

The balance between neural stem cell proliferation and neuronal differentiation is paramount for the appropriate development of the nervous system. Sonic hedgehog (Shh) is known to sequentially promote cell proliferation and specification of neuronal phenotypes, but the signaling mechanisms responsible for the developmental switch from mitogenic to neurogenic have remained unclear. Here, we show that Shh enhances Ca activity at the neural cell primary cilium of developing embryos through Ca influx via transient receptor potential cation channel subfamily C member 3 (TRPC3) and release from intracellular stores in a developmental stage-dependent manner.

WDFY3 mutation alters laminar position and morphology of cortical neurons.

Background: Proper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs).

Wdfy3 regulates glycophagy, mitophagy, and synaptic plasticity.

Autophagy is essential to cell function, as it enables the recycling of intracellular constituents during starvation and in addition functions as a quality control mechanism by eliminating spent organelles and proteins that could cause cellular damage if not properly removed. Recently, we reported on Wdfy3's role in mitophagy, a clinically relevant macroautophagic scaffold protein that is linked to intellectual disability, neurodevelopmental delay, and autism spectrum disorder. In this study, we confirm our previous report that Wdfy3 haploinsufficiency in mice results in decreased mitophagy with accumulation of mitochondria with altered morphology, but expanding on that observation, we also note decreased mitochondrial localization at synaptic terminals and decreased synaptic density, which may contribute to altered synaptic plasticity.

Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring.

Folate is an essential micronutrient required for both cellular proliferation through de novo nucleotide synthesis and epigenetic regulation of gene expression through methylation. This dual requirement places a particular demand on folate availability during pregnancy when both rapid cell generation and programmed differentiation of maternal, extraembryonic, and embryonic/fetal tissues are required. Accordingly, prenatal neurodevelopment is particularly susceptible to folate deficiency, which can predispose to neural tube defects, or when effective transport into the brain is impaired, cerebral folate deficiency.

Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial Abnormalities.

Neural crest cells (NCCs) comprise a transient progenitor cell population of neuroepithelial origin that contributes to a variety of cell types throughout vertebrate embryos including most mesenchymal cells of the cranial and facial structures. Consequently, abnormal NCC development underlies a variety of craniofacial defects including orofacial clefts, which constitute some of the most common birth defects. We previously reported the generation of () mice that carry a loss-of-function allele of the gene encoding the preribosomal factor Pak1ip1.

Organoids, Assembloids, and Novel Biotechnology: Steps Forward in Developmental and Disease-Related Neuroscience.

In neuroscience research, the efforts to find the model through which we can mimic the in vivo microenvironment of a developing or defective brain have been everlasting. While model organisms are used for over a hundred years, many more methods have been introduced with immortalized or primary cell lines and later induced pluripotent stem cells and organoids to be some of these. As the use of organoids becomes more and more common by many laboratories in biology and neuroscience in particular, it is crucial to deeper understand the challenges and possible pitfalls of their application in research, many of which can be surpassed with the support of state-of-the art bioengineering solutions.

Conjunctivitis as a Sentinel of SARS-CoV-2 Infection: a Need of Revision for Mild Symptoms.

COVID-19 has been declared a pandemic by the World Health Organization on March 11, and since then, more than 3 million cases and a quarter million deaths have occurred due to it. Lately, there is a growing evidence for an ophthalmologic symptom (conjunctivitis) to be connected with the disease. This seems to happen in early stages of the infection by SARS-CoV-2, and thus, it is of major importance to understand the mechanism through which the virus can facilitate such a symptom.

Known drugs and small molecules in the battle for COVID-19 treatment.

COVID-19 has been declared a pandemic by the World Health Organization on March 11th and since then more than 3 million cases and a quarter million deaths have occurred due to it. The urge to find a resultful treatment or cure is now pressing more than any other time since the outbreak of the pandemic. Researchers all over the world from different fields of expertise are trying to find the most suitable drugs, that are already known to treat other diseases, and could tackle the process of SARS-CoV2 through which it invades and replicates in human cells.

Pathogenic WDFY3 variants cause neurodevelopmental disorders and opposing effects on brain size.

The underpinnings of mild to moderate neurodevelopmental delay remain elusive, often leading to late diagnosis and interventions. Here, we present data on exome and genome sequencing as well as array analysis of 13 individuals that point to pathogenic, heterozygous, mostly de novo variants in WDFY3 (significant de novo enrichment P = 0.003) as a monogenic cause of mild and non-specific neurodevelopmental delay.

Beyond autophagy: a novel role for autism-linked Wdfy3 in brain mitophagy.

WD repeat and FYVE domain-containing 3 (WDFY3; also known as Autophagy-Linked FYVE or Alfy) is an identified intellectual disability, developmental delay and autism risk gene. This gene encodes for a scaffolding protein that is expressed in both the developing and adult central nervous system and required for autophagy and aggrephagy with yet unexplored roles in mitophagy. Given that mitochondrial trafficking, dynamics and remodeling have key roles in synaptic plasticity, we tested the role of Wdfy3 on brain bioenergetics by using Wdfy3 mice, the only known Wdfy3 mutant animal model with overt neurodevelopmental anomalies that survive to adulthood.

Lysyl oxidase-like 1 polymorphisms in a southwestern Greek cataract population with pseudoexfoliation syndrome.

Purpose: The aim of this study was to determine the possible association of rs1048661 and rs3825942 single nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 (LOXL1) gene of cataract patients from southwestern Greece with pseudoexfoliation (PEX) syndrome.

Patients And Methods: Ninety-three patients with PEX syndrome and 74 without PEX syndrome were recruited with the principal diagnosis being cataract. LOXL1 SNPs, rs1048661 and rs3825942, were genotyped by using polymerase chain reaction.

CPAP therapy induces favorable short-term changes in epicardial fat thickness and vascular and metabolic markers in apparently healthy subjects with obstructive sleep apnea-hypopnea syndrome (OSAHS).

Background: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor for hypertension, coronary artery disease, and diabetes mellitus. Epicardial fat has been recently recognized as a new risk factor and active participant on cardiometabolic risk. The aim of this study was to assess an independent relationship between sleep apnea severity, metabolic and vascular markers, and epicardial fat, at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy.

Measurement of exhaled alveolar nitrogen oxide in patients with lung cancer: a friend from the past still precious today.

Nitric oxide (NO) is a marker of airway inflammation and indirectly a general indicator of inflammation and oxidative stress. NO is a contributing factor in lung cancer at an early stage and also after chemotherapy treatment of lung cancer. We studied whether exhaled NO levels were altered by three cycles of chemotherapy at diagnosis and after chemotherapy, and whether, directly or indirectly, these changes were related to the course of disease.

Effect of CPAP treatment on endothelial function and plasma CRP levels in patients with sleep apnea.

Background: Continuous positive airway pressure (CPAP) is the most effective method for treating obstructive sleep apnea syndrome (OSAS) and alleviating symptoms. Improved sleep quality with effective CPAP therapy might also contribute to attenuated systemic inflammation and improved endothelial function, with subsequent reduction of cardiovascular risk. The aim of this study was to assess the effect of 3-month CPAP therapy on brachial artery flow-mediated dilation (FMD) and plasma C-reactive protein (CRP) levels in patients with OSAS.

Enhancement of TGF-β signaling responses by the E3 ubiquitin ligase Arkadia provides tumor suppression in colorectal cancer.

TGF-β signaling provides tumor protection against colorectal cancer (CRC). Mechanisms that support its tumor-suppressive properties remain unclear. The ubiquitin ligase Arkadia/RNF111 enhances TGF-β signaling responses by targeting repressors of the pathway for degradation.

Cortisol levels and metabolic parameters in middle- and advanced- age subjects: associations with age.

Background: It has been reported that morning cortisol levels increase with age, although there is some controversy in the literature.

Aim: The aim of this study was to examine associations of cortisol levels with advancing age in an elderly population and investigate possible interactions with metabolic and hormonal parameters.

Subjects And Methods: From 372 subjects initially evaluated, we studied 251 ambulatory subjects aged 51-90 yr, median 71 yr (169 women), all permanent residents of a small town in southern Greece.

Novel influenza A (H1N1) infection vs. common influenza-like illness: a prospective study.

Background: On June 11th, 2009 the World Health Organization (WHO) declared the first influenza pandemic of the 21st century. Data regarding the clinical characteristics and course of this viral infectious disease are still being assessed. The aim of this study was to investigate and compare the possible differences in clinical course and outcome between H1N1-positive [H1N1(+)] and negative [H1N1(-)] patients.

Lower early morning plasma cortisol levels are associated with thyroid autoimmunity in the elderly.

Objectives: Thyroid autoimmunity decreases in the very old. We investigated whether glucocorticoid (GC) activity, which increases in old age, is involved in this process.

Subjects And Methods: A total of 321 ambulatory subjects (age 51-95 years, median 71, 207 female) were studied.